[Inverted papilloma of the nose and paranasal sinuses : Diagnosis, treatment, and malignant transformation]. / Invertiertes Papillom der Nase und Nasennebenhöhlen : Diagnostik, Therapie und maligne Transformation.

Inverted papilloma (IP) are benign tumors that show a locally aggressive behavior, a high rate of recurrence, and a potential for malignant transformation. Specific radiological signs such as hyperostosis at the origin of the IP and convoluted cerebriform patterns, as well as the typical endoscopic aspect, can lead to diagnosis and enable preoperative planning of surgical access and the extent of surgery. Endonasal endoscopic techniques are considered the gold standard and the introduction of extended surgical techniques such as the prelacrimal approach, frontal drillout, or orbital transposition facilitate complete subperiosteal resection with preservation of important physiological structures. There is a risk of synchronous and metachronous squamous cell carcinomas (IP-SCC). Research focuses on radiological criteria to differentiate benign IP from IP-SCC, genetic and epigenetic factors in the process of malignant transformation, and estimation of the risk of IP progressing to IP-SCC.

[Local flap reconstruction techniques after frontal sinus drainage type II and III according to Draf]. / Lokale Lappenplastiken bei der Stirnhöhlendrainage Typ II und III nach Draf.

BACKGROUND: Extended endonasal endoscopic frontal sinus surgery is characterized by bone resection beyond the lamellae of the frontal sinus and is currently classified according to Draf as type IIa, type IIb, modified type III (also referred to as type IIc), and type III. This approach is indicated when the surgical goal cannot be achieved through complete removal of the anterior ethmoidal cells. Numerous studies indicate restenosis rates ranging from 7 to 36%, despite creation of maximal openings. Exposed bone, which tends to epithelize slowly with significant crusting and the risk of uncontrolled wound healing depending on the local environment and other factors, is considered a contributing factor. Covering the exposed bone with mucosa can significantly reduce the risk of restenosis. METHODS AND RESULTS: A variety of flap techniques for frontal sinus drainage in Draf III procedures are presented, including some variants that were part of presentations at the 2023 Congress of the European Rhinologic Society in Sofia, Bulgaria. These include combinations of free mucosal grafts, pedicled mucosal flaps, and hybrids combining both techniques. Additionally, the results of current studies are presented. CONCLUSION: The results and achieved opening areas in contemporary Draf III surgeries are significantly improved and larger compared to the early stages of these procedures. A multitude of published studies consistently demonstrate that outcomes are markedly improved with mucosal coverage. Depending on the prevailing anatomy, mucosal conditions, and the extent of the surgical intervention, the most suitable technique should be selected. Therefore, proficiency in various methods is crucial. The use of a flap technique (free, pedicled, or combinations thereof) should be defined as the standard when performing extended frontal sinus surgery (Draf IIb, IIc, III, or endonasal frontal sinus surgery [EFSS] 4-6).

["Radical" versus "functional" surgery of the paranasal sinuses-A contradiction?] / "Radikale" vs. "funktionelle" Chirurgie der Nasennebenhöhlen ­ ein Widerspruch?

BACKGROUND AND OBJECTIVE: The terms "functional" and "radical" paranasal sinus surgery were often considered to be different operations which were mutually exclusive. This overview aims to look at the basics of these terms and surgical procedures and to work out the resulting surgical concepts for clinically relevant indications. MATERIAL AND METHODS: Selective literature analysis using the data base PubMed, corresponding textbooks and resulting secondary literature regarding functional and radical or extended paranasal sinus surgery. Similarly, the current literature regarding clinically relevant indications for sinus surgery were analyzed. RESULTS AND CONCLUSION: Modern pathophysiological knowledge, anatomically and pathophysiologically substantiated endoscopic surgical procedures and the usage of up to date technical possibilities have resulted in concepts which combine functional and so-called radical or extended surgery of the paranasal sinuses that complement each other and sometimes even overlap. The preoperative diagnosis and definition of underlying diseases are decisive and should be as precise as possible, as the extent and surgical details mainly depend on them: a sole creation of free drainage pathways, an additional creation of anatomical access for subsequent topical treatment or a complete (radical) removal of a pathological process.

[Decision-making in the treatment of chronic rhinosinusitis with nasal polyps in the era of biologics]. / Entscheidungsfindung bei der Behandlung der chronischen Rhinosinusitis mit Nasenpolypen in der Ära der Biologika.

Chronic rhinosinusitis is one of the most common chronic diseases in the population. Chronic rhinosinusitis with nasal polyps (CRSwNP) in adults is predominantly characterized by a type 2 inflammatory endotype. If sufficient control cannot be achieved through primary drug therapy, surgical intervention is usually recommended as the next stage of treatment. Nowadays, various biologics are available that have been or will be approved for use in these patients. This review summarizes the presentations from the 29th Congress of the European Rhinologic Society in Sofia 2023 and the latest findings on decision-making in the treatment of CRSwNP. Standard therapy with medication and sinus surgery fails in some patients with CRSwNP. Biologics that act on the type 2 inflammatory pathway led to a reduction in the nasal polyp score (NPS), an improvement in nasal obstruction, and an improvement in quality of life without significant side effects. Biomarkers such as total IgE, serum eosinophils, and Osteoprotegerin (OPG) can provide indications of the success of the treatment. In summary, it can be said that for many patients with recurrent CRSwNP, a combination of paranasal sinus surgery and treatment with a biologic that is precisely tailored to the patient's endotype is the best option. However, the question of which surgical approach and which biologic at which time and for which patient is still ongoing and requires further studies.

[Fundamentals and practice of the application of nasal packing in sinonasal surgery]. / Grundlagen und Praxis der Anwendung von Nasentamponaden in der endonasalen Chirurgie.

BACKGROUND AND OBJECTIVES: This paper presents an overview on nasal packing materials which are available in Germany. The current literature is analyzed whether there are robust criteria regarding use nasal packing after sinonasal surgery, whether there are fundamental and proven advantages or disadvantages of products, and what this means in clinical practice. MATERIALS AND METHODS: Selective literature analysis using the PubMed database (key words "nasal packing", "nasal tamponade", "nasal surgery", "sinonasal surgery", or "sinus surgery"), corresponding text books and resulting secondary literature. RESULTS AND CONCLUSIONS: Because of systematic methodological shortcomings, the literature does not help in the decision-making about which nasal packing should be used after which kind of sinonasal surgery. In fact, individual approaches for the many different clinical scenarios are recommended. In principle, nasal packing aims in hemostasis, should promote wound healing, and should not result in secondary morbidity. Nasal packing materials should be smooth (non-absorbable materials), inert (absorbable materials), and should not exert excessive pressure. Using non-absorbable packing entails the risk of potentially lethal aspiration and ingestion. For safety reasons inpatient control is recommended as long as this packing is in situ. With other, uncritical packing materials and in patients with special conditions, outpatient control could be justified.

Polygenic Risk Scores for Prediction of Subclinical Coronary Artery Disease in Persons With Human Immunodeficiency Virus (HIV): The Swiss HIV Cohort Study.

BACKGROUND: In people with human immunodeficiency virus (HIV) (PWH), individual polygenic risk scores (PRSs) are associated with coronary artery disease (CAD) events. Whether PRSs are associated with subclinical CAD is unknown. METHODS: In Swiss HIV Cohort Study participants of European descent, we defined subclinical CAD as presence of soft, mixed, or high-risk plaque (SMHRP) on coronary computed tomography (CT) angiography, or as participants in the top tertile of the study population's coronary artery calcium (CAC) score, using noncontrast CT. We obtained univariable and multivariable odds ratios (ORs) for subclinical CAD endpoints based on nongenetic risk factors, and validated genome-wide PRSs built from single nucleotide polymorphisms associated with CAD, carotid intima-media thickness (IMT), or longevity in the general population. RESULTS: We included 345 genotyped participants (median age, 53 years; 89% male; 96% suppressed HIV RNA); 172 and 127 participants had SMHRP and CAC, respectively. CAD-associated PRS and IMT-associated PRS were associated with SMHRP and CAC (all P < .01), but longevity PRS was not. Participants with unfavorable CAD-PRS (top quintile) had an adjusted SMHRP OR = 2.58 (95% confidence interval [CI], 1.18-5.67), and a CAC OR = 3.95 (95% CI, 1.45-10.77) vs. bottom quintile. Unfavorable nongenetic risk (top vs. bottom quintile) was associated with adjusted SMHRP OR = 24.01 (95% CI, 9.75-59.11), and a CAC-OR = 65.07 (95% CI, 18.48-229.15). Area under the receiver operating characteristic curve increased when we added CAD-PRS to nongenetic risk factors (SMHRP: 0.75 and 0.78, respectively; CAC: 0.80 and 0.83, respectively). CONCLUSIONS: In Swiss PWH, subclinical CAD is independently associated with an individual CAD-associated PRS. Combining nongenetic and genetic cardiovascular risk factors provided the most powerful subclinical CAD prediction.

Partial Maxillectomy for the Improvement of Nasal Obstruction Can Be Combined with Septorhinoplasty.

We describe the (anteromedial) partial maxillectomy technique which can be used to address impaired nasal breathing in cases of significant protrusion of the frontal process of the maxilla into the nasal cavity, narrowing the nasal pathway. It fits to nasal physiology avoiding mucosal resection. It can be combined with surgery of the inferior turbinate. The described technique can be used in all forms of rhinoplasty.

[The Less Frequent Tick-borne Infections in Central Europe]. / Die anderen Zecken-übertragenen Infektionen in Mitteleuropa.

The Less Frequent Tick-borne Infections in Central Europe Abstract. The incidence of tick-borne infections is increasing, the endemic areas of tick vectors are expanding, novel tick-borne pathogens have been identified, and known pathogens are emerging in new geographic areas. This review focuses on the less frequent tick-borne pathogens in Central Europe, including Anaplasma, Babesia, Borrelia miyamotoi, Candidatus Neoehrlichia mikurensis, Ehrlichia, Francisella tularensis, Rickettsia, relapsing fever spirochetes, and tick-borne viruses. Travel-associated infections are also considered emphasizing a clinical and geographic approach. In addition to the most frequent Ixodes sp. also other tick species transmitting human pathogens are endemic in Europe. Clinicians should maintain suspicion for tick-borne diseases in patients presenting with fever of unexplained cause, with acute rash or with febrile neurological signs and symptoms. Because clinical manifestations of tick-borne infections are nonspecific - except for Erythema migrans - it is important to consider tick-borne illnesses even without a reported tick exposure or a suggesting travel history. Less than 50% of infected patients are aware of a tick-bite. Patients' history must include profession, leisure time activities, travel, and immune status. Tick-borne diseases may have a severe and life-threatening course in immunocompromised and splenectomized persons.

Impact of an electronic alert on prescription patterns of meropenem, voriconazole and caspofungin.

BACKGROUND: Antimicrobial stewardship programs promote the appropriate use of antimicrobial substances through the implementation of evidence-based, active and passive interventions. We analyzed the effect of a computer-assisted intervention on antimicrobial use in a tertiary care hospital. METHODS: Between 2011 and 2016 we introduced an electronic alert for patients being prescribed meropenem, voriconazole and caspofungin. At prescription and at day 3 of treatment, physicians were informed about the risk related to these antimicrobial substances by an electronic alert in the medical records. Physicians were invited to revoke or confirm the prescription and to contact the infectious disease (ID) team. Using interrupted time series regression, the days of therapy (DOTs) and the number of prescriptions before and after the intervention were compared. RESULTS: We counted 64,281 DOTs for 5549 prescriptions during 4100 hospital stays. Overall, the DOTs decreased continuously over time. An additional benefit of the alert could not be observed. Similarly, the number of prescriptions decreased over time, without significant effect of the intervention. When considering the three drugs separately, the alert impacted the duration (change in slope of DOTs/1000 bed days; P = 0.0017) as well as the number of prescriptions (change in slope of prescriptions/1000 bed days; P < 0.001) of voriconazole only. CONCLUSIONS: The introduction of the alert lowered prescriptions of voriconazole only. Thus, self-stewardship alone seems to have a limited impact on electronic prescriptions of anti-infective substances. Additional measures such as face-to-face prompting with ID physicians or audit and feedback are indispensable to optimize antimicrobial use.

[Postoperative treatment following paranasal sinus surgery]. / Postoperative Versorgung bei Nasennebenhöhleneingriffen.

Postoperative care is a crucial aspect for the success of paranasal sinus interventions. Basic procedures include saline nasal wash, which should be started on the first postoperative day, topical steroids, and antibiotics in cases of infection. Medical treatment involves aspiration of secretion in the inferior meatus during the first week. Removal of scabs in the surgical field should be carried out under endoscopic control beginning at the second week. Intervals are scheduled individually. Occlusion of the nose for the time of epithelium regeneration provides a moist space in the ethmoid, which improves wound healing.

Antiretroviral Drugs Associated With Subclinical Coronary Artery Disease in the Swiss Human Immunodeficiency Virus Cohort Study.

BACKGROUND: Coronary artery disease (CAD) events have been associated with certain antiretroviral therapy (ART) agents. In contrast, the influence of ART on subclinical atherosclerosis is not clear. The study objective was to assess the association between individual ART agents and the prevalence and extent of subclinical CAD. METHODS: Coronary artery calcium (CAC) scoring and coronary computed tomography angiography (CCTA) were performed in ≥45-year-old Swiss Human Immunodeficiency Virus Cohort Study participants. The following subclinical CAD endpoints were analyzed separately: CAC score >0, any plaque, calcified plaque, noncalcified/mixed plaque, segment involvement score (SIS), and segment severity score (SSS). Logistic regression models calculated by inverse probability of treatment weights (IPTW) were used to explore associations between subclinical CAD and cumulative exposure to the 10 most frequently used drugs. RESULTS: There were 403 patients who underwent CCTA. A CAC score >0 was recorded in 188 (47%), any plaque in 214 (53%), calcified plaque in 151 (38%), and noncalcified/mixed plaque in 150 (37%) participants. A CAC score >0 was negatively associated with efavirenz (IPTW adjusted odds ratio per 5 years 0.73, 95% confidence interval [CI] 0.56-0.96), tenofovir disoproxil fumarate (0.68, 95% CI 0.49-0.95), and lopinavir (0.64, 95% CI 0.43-0.96). Any plaque was negatively associated with tenofovir disoproxil fumarate (0.71, 95% CI 0.51-0.99). Calcified plaque was negatively associated with efavirenz (0.7, 95% CI 0.57-0.97). Noncalcified/mixed plaque was positively associated with abacavir (1.46, 95% CI 1.08-1.98) and negatively associated with emtricitabine (0.67, 95% CI 0.46-0.99). For SSS and SIS, we found no association with any drug. CONCLUSIONS: An increased risk of noncalcified/mixed plaque was only found in patients exposed to abacavir. Emtricitabine was negatively associated with noncalcified/mixed plaque, while tenofovir disoproxil fumarate and efavirenz were negatively associated with any plaque and calcified plaque, respectively.

Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study.

BACKGROUND: The level of evidence for HIV transmission risk through condomless sex in serodifferent gay couples with the HIV-positive partner taking virally suppressive antiretroviral therapy (ART) is limited compared with the evidence available for transmission risk in heterosexual couples. The aim of the second phase of the PARTNER study (PARTNER2) was to provide precise estimates of transmission risk in gay serodifferent partnerships. METHODS: The PARTNER study was a prospective observational study done at 75 sites in 14 European countries. The first phase of the study (PARTNER1; Sept 15, 2010, to May 31, 2014) recruited and followed up both heterosexual and gay serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex, whereas the PARTNER2 extension (to April 30, 2018) recruited and followed up gay couples only. At study visits, data collection included sexual behaviour questionnaires, HIV testing (HIV-negative partner), and HIV-1 viral load testing (HIV-positive partner). If a seroconversion occurred in the HIV-negative partner, anonymised phylogenetic analysis was done to compare HIV-1 pol and env sequences in both partners to identify linked transmissions. Couple-years of follow-up were eligible for inclusion if condomless sex was reported, use of pre-exposure prophylaxis or post-exposure prophylaxis was not reported by the HIV-negative partner, and the HIV-positive partner was virally suppressed (plasma HIV-1 RNA <200 copies per mL) at the most recent visit (within the past year). Incidence rate of HIV transmission was calculated as the number of phylogenetically linked HIV infections that occurred during eligible couple-years of follow-up divided by eligible couple-years of follow-up. Two-sided 95% CIs for the incidence rate of transmission were calculated using exact Poisson methods. FINDINGS: Between Sept 15, 2010, and July 31, 2017, 972 gay couples were enrolled, of which 782 provided 1593 eligible couple-years of follow-up with a median follow-up of 2·0 years (IQR 1·1-3·5). At baseline, median age for HIV-positive partners was 40 years (IQR 33-46) and couples reported condomless sex for a median of 1·0 years (IQR 0·4-2·9). During eligible couple-years of follow-up, couples reported condomless anal sex a total of 76 088 times. 288 (37%) of 777 HIV-negative men reported condomless sex with other partners. 15 new HIV infections occurred during eligible couple-years of follow-up, but none were phylogenetically linked within-couple transmissions, resulting in an HIV transmission rate of zero (upper 95% CI 0·23 per 100 couple-years of follow-up). INTERPRETATION: Our results provide a similar level of evidence on viral suppression and HIV transmission risk for gay men to that previously generated for heterosexual couples and suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero. Our findings support the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV. FUNDING: National Institute for Health Research.

The Effect of Hopelessness and Perceived Group Compatibility on Treatment Outcome for Patients With Personality Dysfunction.

Improvement in life satisfaction is hard to achieve for any patient with personality psychopathology, and possibly even moreso for those who feel hopeless at the start of treatment. The present research investigated the potential influence of hopelessness in the treatment of patients with personality dysfunction, using data from patients who completed an intensive group therapy program designed to reduce symptom distress and support optimal psychosocial functioning (N = 80). In the present study, we sought to examine whether hopelessness would moderate (i.e., strengthen or weaken) relations between compatibility ratings and life satisfaction outcome. Hopelessness had a significant moderating effect on the relationship between compatibility and outcome, suggesting that, for patients who entered treatment feeling more hopeless, higher appraisals of fit within the group facilitated better gains in life satisfaction. If replicated, the findings underlie the importance of focusing on increasing hope and perceived group affiliation in the treatment of personality dysfunction.

Sonicate fluid inoculated into blood culture bottles does not improve diagnosis of periprosthetic joint infection caused by anaerobes. A retrospective analysis.

BACKGROUND: In microbiological diagnosis of periprosthetic joint infection (PJI) there is much controversial discussion about culture media and incubation time, especially if anaerobic bacteria are the causative agents. This retrospective analysis was conducted to compare the results obtained by inoculation of sonicate fluid from prosthetic components into BD Bactec blood culture bottles with those obtained by our culture method using sensitive supplemented growth media. METHODS: Twenty-eight cases were included in this study. For definition of PJI, the criteria of the Musculoskeletal Infection Society (MSIS) were considered. The quantity and time to positivity of anaerobes detected in sonicate fluid were monitored both from inoculated supplemented liver thioglycollate broth and anaerobic blood culture bottles. Furthermore, phenotypic testing was performed on the antimicrobial activity within the sonicate fluid. RESULTS: The most frequently isolated microbes were Cutibacterium species, followed by Finegoldia magna, Parvimonas micra, Robinsoniella peoriensis, Clostridium species, Peptoniphilus harei and Slackia exigua. In 24 cases, the microorganisms became detectable within five days (median time 3.2 days) when sonicate fluid was incubated in supplemented liver thioglycollate broth, regardless of whether the patients had taken antimicrobial agents prior to surgery. However, when sonicate fluid was inoculated into anaerobic Bactec bottles, the median time to positivity was 7.4 days and only 12 cases (43%) were correctly identified. Sixteen cases remained negative after 14 days of incubation. CONCLUSION: Depending on the pathogen, incubation of sonicate fluid using blood culture bottles can support diagnosis of PJI but compared with our culture medium it is less efficient if anaerobes are the suspected cause of infection. Microbiological expertise is therefore indispensable to ensure reliable detection of these microorganisms in PJI until a gold standard for laboratory handling of anaerobes has been established.

[Breast Cancer in Men - Health Care Professionals' Perspectives on the Multidisciplinary Care of a Rare Disease]. / Brustkrebs beim Mann ­ die Sicht der beteiligten Berufsgruppen auf die multiprofessionelle Versorgung einer seltenen Erkrankung.

AIM OF THE STUDY: Male breast cancer is a rare disease, for which, however, available care is from highly specialized care structures intended for female patients. So far, it is unknown whether the focus of care structures for women leads to deficits in the care for men. Therefore, the aim of the present study was to identify possible deficits in male breast cancer care from the perspective of the health care professions involved. METHODS: Semi-structured interviews with n=23 participants and 2 focus group discussions with n=7 and n=9 participants were conducted. The transcripts of the interviews and focus group discussions were analyzed by qualitative content analysis using MAXQDA. RESULTS: Some participants felt insecure and uniformed in terms of treatment recommendations for men with breast cancer. Often, responsibilities were vague or unknown. Many participants felt a lack of interdisciplinary cooperation, especially in follow-up care. Some respondents complained of a lack of rehabilitation centers for men with breast cancer. CONCLUSION: Male breast cancer patients benefit from the advanced structures for breast cancer care. However, some health care problems were identified. Our results together with representative data can help develop practical recommendations for improving the quality of care of male breast cancer patients.

Improving social functioning and life satisfaction among patients with personality dysfunction: Connectedness and engagement in integrative group treatment.

Reduced social impairment and improved life satisfaction are important objectives in group treatment for patients with personality dysfunction. Knowledge regarding patient characteristics and group treatment processes that contribute to these outcomes, however, remains limited. Dispositional connectedness, the valuing of interpersonal connections, may be an important patient factor that influences patients' experience of group treatment in ways that facilitate therapeutic benefits. The present study investigated the roles of dispositional connectedness and group engagement in contributing to improvement in social functioning and life satisfaction through integrative group treatment for personality dysfunction. Seventy-nine patients who completed an integrative group treatment programme were assessed for dispositional connectedness at baseline and social functioning and life satisfaction at pretreatment and posttreatment; each also provided ratings of group engagement during treatment. Regression analyses using bootstrap confidence intervals found significant indirect effects for dispositional connectedness regarding improvement in both social functioning and life satisfaction, through the mediating effect of group engagement. Thus, patients who entered treatment with tendencies towards interpersonal connectedness perceived a higher level of engagement in the group environment. Group engagement in turn contributed to greater improvement in social functioning and to greater improvement in life satisfaction following treatment. The findings indicate dispositional connectedness as a salient characteristic in selecting patients for group treatment and highlight the role of an engaged interpersonal climate in facilitating improvement in social functioning and life satisfaction.

Cessation of Cigarette Smoking and the Impact on Cancer Incidence in Human Immunodeficiency Virus-infected Persons: The Data Collection on Adverse Events of Anti-HIV Drugs Study.

Background: Cancers are a major source of morbidity and mortality for human immunodeficiency virus (HIV)-infected persons, but the clinical benefits of smoking cessation are unknown. Methods: Participants were followed from 1 January 2004 until first cancer diagnosis, death, or 1 February 2016. Smoking status was defined as ex-smoker, current smoker, and never smoker. Adjusted incidence rate ratios (aIRRs) were calculated using Poisson regression, adjusting for demographic and clinical factors. Results: In total 35442 persons from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study contributed 309803 person-years of follow-up. At baseline, 49% were current smokers, 21% were ex-smokers, and 30% had never smoked. Incidence of all cancers combined (n = 2183) was highest <1 year after smoking cessation compared to never smokers (aIRR, 1.66 [95% confidence interval {CI}, 1.37-2.02]) and not significantly different from never smokers 1-1.9 years after cessation. Lung cancer incidence (n = 271) was elevated <1 year after cessation (aIRR, 19.08 [95% CI, 8.10-44.95]) and remained 8-fold higher 5 years after smoking cessation (aIRR, 8.69 [95% CI, 3.40-22.18]). Incidence of other smoking-related cancers (n = 622) was elevated in the first year after cessation (aIRR, 2.06 [95% CI, 1.42-2.99]) and declined to a level similar to nonsmokers thereafter. Conclusions: Lung cancer incidence in HIV-infected individuals remained elevated >5 years after smoking cessation. Deterring uptake of smoking and smoking cessation efforts should be prioritised to reduce future cancer risk.

The TransFLUas influenza transmission study in acute healthcare - recruitment rates and protocol adherence in healthcare workers and inpatients.

BACKGROUND: Detailed knowledge about viral respiratory disease transmission dynamics within healthcare institutions is essential for effective infection control policy and practice. In the quest to study viral transmission pathways, we aimed to investigate recruitment rates and adherence of healthcare workers (HCWs) and hospital inpatients with a study protocol that involves prospective surveillance based on daily mid-turbinate nasal swabs and illness diaries. METHODS: Single center prospective surveillance of patients and HCWs in three different hospital departments of a tertiary care center during an entire influenza season in Switzerland. Inpatients and acute care HCWs were asked to provide mid-turbinate nasal swabs and illness diaries on a daily basis. Study protocol adherence and recruitment rates were the primary outcomes of interest. RESULTS: A total 251 participants (59 (23.5%) health care workers and 192 (76.5%) inpatients) were recruited from three different hospital wards. Recruitment rates differed between HCWs (62.1% of eligible HCWs) and inpatients (32.5%; P < 0.001), but not within HCWs (P = 0.185) or inpatients (P = 0.301) of the three departments. The total number of study-days was 7874; 2321 (29.5%) for inpatients and 5553 (70.5%) for HCWs. HCWs were followed for a median of 96 days (range, 71-96 days) and inpatients for 8 days (range, 3-77 days). HCWs provided swabs on 73% (range, 0-100%) of study days, and diaries on 77% (range 0-100%). Inpatients provided swabs and diaries for 83% (range, 0-100%) of days in hospital. In HCWs, increasing age, working in internal medicine and longer duration of total study participation were positively associated with the proportion of swabs and diaries collected. Adherence to the study protocol was significantly lower in physicians as compared to nurses for both swabs (P = 0.042) and diaries (P = 0.033). In inpatients, no association between demographic factors and adherence was detected. Conclusions Prospective surveillance of respiratory viral disease was feasible in a cohort of inpatients and HCWs over an entire influenza season, both in terms of recruitment rates and adherence to a study protocol that included daily specimen collection and illness diaries. TRIAL REGISTRATION: clinicaltrials.gov NCT02478905 . Date of registration June 23, 2015.

In Vivo and in Vitro Proteome Analysis of Human Immunodeficiency Virus (HIV)-1-infected, Human CD4+ T Cells.

Host-directed therapies against HIV-1 are thought to be critical for long term containment of the HIV-1 pandemic but remain elusive. Because HIV-1 infects and manipulates important effectors of both the innate and adaptive immune system, identifying modulations of the host cell systems in humans during HIV-1 infection may be crucial for the development of immune based therapies. Here, we quantified the changes of the proteome in human CD4+ T cells upon HIV-1 infection, both in vitro and in vivo A SWATH-MS approach was used to measure the proteome of human primary CD4+ T cells infected with HIV-1 in vitro as well as CD4+ T cells from HIV-1-infected patients with paired samples on and off antiretroviral treatment. In the in vitro experiment, the proteome of CD4+ T cells was quantified over a time course following HIV-1 infection. 1,725 host cell proteins and 4 HIV-1 proteins were quantified, with 145 proteins changing significantly during the time course. Changes in the proteome peaked 24 h after infection, concomitantly with significant HIV-1 protein production. In the in vivo branch of the study, CD4+ T cells from viremic patients and those with no detectable viral load after treatment were sorted, and the proteomes were quantified. We consistently detected 895 proteins, 172 of which were considered to be significantly different between the viremic patients and patients undergoing successful treatment. The proteome of the in vitro-infected CD4+ T cells was modulated on multiple functional levels, including TLR-4 signaling and the type 1 interferon signaling pathway. Perturbations in the type 1 interferon signaling pathway were recapitulated in CD4+ T cells from patients. The study shows that proteome maps generated by SWATH-MS indicate a range of functionally significant changes in the proteome of HIV-infected human CD4+ T cells. Exploring these perturbations in more detail may help identify new targets for immune based interventions.

Subclinical coronary artery disease in Swiss HIV-positive and HIV-negative persons.

Aims: HIV-positive persons have increased cardiovascular event rates but data on the prevalence of subclinical atherosclerosis compared with HIV-negative persons are not uniform. We assessed subclinical atherosclerosis utilizing coronary artery calcium (CAC) scoring and coronary computed tomography angiography (CCTA) in 428 HIV-positive participants of the Swiss HIV Cohort Study and 276 HIV-negative controls concurrently referred for clinically indicated CCTA. Methods and results: We assessed the association of HIV infection, cardiovascular risk profile, and HIV-related factors with subclinical atherosclerosis in univariable and multivariable analyses. HIV-positive participants (median duration of HIV infection, 15 years) were younger than HIV-negative participants (median age 52 vs. 56 years; P < 0.01) but had similar median 10-year Framingham risk scores (9.0% vs. 9.7%; P = 0.40). The prevalence of CAC score >0 (53% vs. 56.2%; P = 0.42) and median CAC scores (47 vs. 47; P = 0.80) were similar, as was the prevalence of any, non-calcified/mixed, and high-risk plaque. In multivariable adjusted analysis, HIV-positive participants had a lower prevalence of calcified plaque than HIV-negative participants [36.9% vs. 48.6%, P < 0.01; adjusted odds ratio (aOR) 0.57; 95% confidence interval (CI) 0.40-0.82; P < 0.01], lower coronary segment severity score (aOR 0.72; 95% CI 0.53-0.99; P = 0.04), and lower segment involvement score (aOR 0.71, 95% CI 0.52-0.97; P = 0.03). Advanced immunosuppression was associated with non-calcified/mixed plaque (aOR 1.97; 95% CI 1.09-3.56; P = 0.02). Conclusion: HIV-positive persons in Switzerland had a similar degree of non-calcified/mixed plaque and high-risk plaque, and may have less calcified coronary plaque, and lower coronary atherosclerosis involvement and severity scores than HIV-negative persons with similar Framingham risk scores.